A Novel VACTERL Assessment Tool to Facilitate Counseling for Expectant Families.

INTRODUCTION: VACTERL is defined as 3 or more of the following congenital defects: vertebral, anorectal, cardiac, tracheoesophageal (TE), renal, and limb. The purpose of this study was to create an easy-to-use assessment tool to help providers counsel expecting families regarding the likelihood of additional anomalies and postnatal outcomes. METHODS: Employing the Kids' Inpatient Database from 2003-2016, neonates (<29 days old) with VACTERL were identified using ICD-9-CM and ICD-10-CM codes. For each unique combination of VACTERL, multivariable logistic regression was used to estimate inpatient mortality, and Poisson regression was used to estimate length-of-stay during the initial hospitalization. RESULTS: The assessment tool used in this study is available at https://choc-trauma.shinyapps.io/VACTERL. 1,886 of 11,813,782 (0.016%) neonates presented with VACTERL. 32% weighed <1,750 g, and 239 (12.7%) died prior to discharge. Associated with mortality were limb anomaly (1.8 [1.01-3.22], p < 0.05), prematurity (1.99 [1.14-3.47], p < 0.02), and weight <1,750 g (2.19 [1.25-3.82], p < 0.01). Median length-of-stay was 14 days (IQR: 7-32). Associated with increased length-of-stay were cardiac defect (1.47 [1.37-1.56], p < 0.001), vertebral anomaly (1.1 [1.05-1.14], p < 0.001), TE fistula (1.73 [1.66-1.81], p < 0.001), anorectal malformation (1.12 [1.07-1.16], p < 0.001), and weight <1,750 g (1.65 [1.57-1.73], p < 0.001). CONCLUSION: This novel assessment tool may help providers counsel families confronting a VACTERL diagnosis.

Extreme enhanced myometrial vascularity following cesarean scar pregnancy: a new diagnostic entity.

OBJECTIVE: To define, illustrate and to follow-up the diagnosis, pathophysiology and treatment of a subset of the known enhanced myometrial vascularity (EMV): its extreme form, associated with cesarean scar pregnancies (CSP) and with some cases pf placenta accreta spectrum being at increased risk of significant bleeding complications. We also aim to provide guidance to the management of such cases. MATERIAL AND METHODS: This is an IRB-approved retrospective observational study of thirteen patients with an extreme form of EMV complicating CSPs. Patient's age, parity, number of cesarean deliveries, initial and time to negative serum hCG levels, primary and secondary diagnoses, blood flow peak systolic velocities, primary and secondary treatments, uterine artery embolization and outcomes were recorded. RESULTS: Gestational ages ranged 6-11 weeks at initial presentation. Initial serum hCG was 20.0-102.48 mIU/L (mean 44.4 mIU/L). Diameter of EMV reached 20-75 mm (mean 46.8 mm). The mean peak systolic velocity (PSV) was 84.2 cm/s (range 46.7-118.0). Primary treatments were: systemic methotrexate (MTX) alone; D&C alone; MTX and D&C; local and systemic intra-gestational MTX injection; double cervical ripening balloon with systemic MTX; misoprostol and D&C; emergent UAE. UAE and hysterectomy were the two main secondary treatments in 10 women except 1 having a D&C after UAE, and in 1 the lesion regressed without secondary treatment. Mean time to nonpregnant hCG levels was 21-122 days (mean 67.2). Mean follow-up was 110.2 days (range 26-160). Ten women were treated with UAE, 6 had one, 3 had two embolizations. Two women had hysterectomies, one of these for persistent bleeding. Based upon the common denominators of the clinical and the US pictures, our definition of extreme EMV is sustained form of EMV associated with treated or untreated CSP, with peak systolic velocities of blood flow over 50 cm/s, slow return or plateauing serum hCG, with or without clinically significant vaginal bleeding, unresponsive to initial or secondary treatment requiring uterine artery embolization or hysterectomy. CONCLUSION: The EMV developing in the background of retained placental tissue associated with CSP differs following the normal regression of the physiologically re-modelled, dilated vascular bed from the faulty "disrepair" of the vessel wall in in treated or untreated CSPs. The "threatening" appearance of the above EMVs warranted the term "extreme", creating their separate new sub-category." Extreme forms of CSP-related EMV pose significant diagnostic and management challenges. Prompt recognition and intervention, the proactive use of UAE, can maximize the outcome of women affected by this "extreme" form of EMV enabling to preserve reproductive potential. Obstetricians, gynecologists and interventional radiologists should be aware of this form of severe vascular complication.

Sex Differences in Mortality Rates and Underlying Conditions for COVID-19 Deaths in England and Wales.

OBJECTIVE: To address the issue of limited national data on the prevalence and distribution of underlying conditions among COVID-19 deaths between sexes and across age groups. PATIENTS AND METHODS: All adult (≥18 years) deaths recorded in England and Wales (March 1, 2020, to May 12, 2020) were analyzed retrospectively. We compared the prevalence of underlying health conditions between COVID and non-COVID-related deaths during the COVID-19 pandemic and the age-standardized mortality rate (ASMR) of COVID-19 compared with other primary causes of death, stratified by sex and age group. RESULTS: Of 144,279 adult deaths recorded during the study period, 36,438 (25.3%) were confirmed COVID deaths. Women represented 43.2% (n=15,731) of COVID deaths compared with 51.9% (n=55,980) in non-COVID deaths. Overall, COVID deaths were younger than non-COVID deaths (82 vs 83 years). ASMR of COVID-19 was higher than all other common primary causes of death, across age groups and sexes, except for cancers in women between the ages of 30 and 79 years. A linear relationship was observed between ASMR and age among COVID-19 deaths, with persistently higher rates in men than women across all age groups. The most prevalent reported conditions were hypertension, dementia, chronic lung disease, and diabetes, and these were higher among COVID deaths. Pre-existing ischemic heart disease was similar in COVID (11.4%) and non-COVID (12%) deaths. CONCLUSION: In a nationwide analysis, COVID-19 infection was associated with higher age-standardized mortality than other primary causes of death, except cancer in women of select age groups. COVID-19 mortality was persistently higher in men and increased with advanced age.

Risk of donor demise after laser therapy for twin-twin transfusion when complicated by growth discordance and abnormal umbilical artery Doppler findings.

OBJECTIVE: To investigate the natural course of abnormal umbilical artery Doppler (UAD) findings in donor fetuses after laser surgery and the prognostic significance of resolution, persistence, or new onset UAD abnormalities with and without the presence of preoperative growth discordance. STUDY DESIGN: Retrospective cohort study of all monochorionic-diamniotic multi-fetal gestations diagnosed with twin-twin transfusion syndrome (TTTS) undergoing laser surgery at a single large metropolitan referral center from 2010-2016. The estimated fetal weight was measured preoperatively and the UAD were measured both pre- and postoperatively (median = 8 days). Patients were grouped according to the presence of abnormal UAD with or without growth discordance pre- and postoperatively. Risk ratios (RR) were calculated for each group for risk of intrauterine fetal demise compared to the pre- and postoperative normal UAD groups as the referents. RESULTS: There were eighty-one women who met inclusion criteria throughout the study period. Forty-three (53.1%) patients had abnormal donor twin UAD preoperatively and 33 (40.7%) were diagnosed with growth discordance. However, 13 (44.8%) had normalization of the UAD postoperatively (median = 8 days) with a similar rate of donor fetal demise as the non-discordant preoperative normal UAD group (7.7% versus 10.3%, p = .79). Abnormal preoperative UAD was associated with an increased risk of donor demise (RR 3.6, CI 1.1-12.1), which was further elevated in the presence of growth discordance (RR 5.2, CI 1.7-16.3). The greatest risk for donor demise was seen if the UAD remained abnormal postoperatively with concomitant growth discordance (RR 10.3, CI 2.5-41.6). CONCLUSIONS: Preoperative abnormal donor UAD is a significant risk for donor demise post-laser therapy for TTTS. Persistent postoperative abnormal UAD with concomitant growth discordance confers the greatest risk for donor demise. However, resolution of abnormal UAD has a similar rate of donor demise when compared to patients with normal UAD preoperatively.

Impact of recipient twin preoperative myocardial performance index in twin-twin transfusion syndrome treated with laser.

OBJECTIVE: To validate the efficacy of laser therapy for twin-twin transfusion syndrome (TTTS) in the treatment of recipient twin cardiomyopathy and investigate whether severity of preoperative cardiomyopathy can predict fetal survival postoperatively. STUDY DESIGN: Retrospective study of monochorionic-diamniotic (MCDA) pregnancies complicated by TTTS treated by selective fetoscopic laser photocoagulation (SFLP) performed between March 2010 and October 2014 at a single center. The recipient right ventricular (RV) and left ventricular (LV) myocardial performance index (MPI) were measured both pre- and postoperatively. The data were analyzed with the Wilcoxon signed rank and parametric t-tests. RESULTS: Forty-three women met inclusion criteria during the study period. There was a substantial improvement in recipient LV (0.57 ± 0.13 versus 0.43 ± 0.13, p ≤ 0.0001) and RV (0.60 ± 0.16 versus 0.49 ± 0.18, p ≤ 0.0001) MPI postoperatively (median = 8 days). Recipient preoperative LV and RV MPI did not correlate with recipient or donor survival at 24 hours, 7 days or at birth. Thirty-seven recipients (95%) showed improvement in either LV or RV MPI and 22 (56%) showed complete resolution of cardiac dysfunction. CONCLUSION: Laser treatment for TTTS causes rapid improvement in the cardiac function of recipient fetuses. The severity of recipient preoperative MPI does not correlate with survival of either twin postoperatively.

Effect of Cervical Length Recovery after Laser Surgery for Twin-Twin Transfusion Syndrome.

Objective To evaluate the impact of polyhydramnios on preoperative cervical length and whether cervical length recovery after amnioreduction during selective fetoscopic laser photocoagulation (SFLP) is associated with a greater gestational age at delivery in pregnancies complicated by twin-twin transfusion syndrome (TTTS). Methods Retrospective study of 50 pregnancies complicated by TTTS treated with SFLP between March 2010 and July 2014 at a single center. Preoperative maximum vertical pocket (MVP) was measured along with pre- and postoperative cervical length. A cervical length difference was calculated, with a difference of ± 3 mm considered no change. Results Only 12 (34%) patients showed an increased cervical length after amnioreduction during laser surgery. There was no statistical difference between either negative or positive change in cervical length groups and mean gestational age at delivery (p = 0.82). There also was no correlation between preoperative MVP and preoperative cervical length (p = 0.36) or gestational age at delivery (p = 0.77). However, there was a statistically shorter mean preoperative cervical length in patients who delivered <32 weeks of gestation (3.62 ± 0.66 vs. 4.20 ± 0.85 cm; p = 0.03). Conclusion Severity of polyhydramnios does not correlate with preoperative cervical length, and variability of the cervix postoperatively does not appear to affect gestational age at delivery.

Microwave Ablation for Twin-Reversed Arterial Perfusion Sequence: A Novel Application of Technology.

INTRODUCTION: Twin-reversed arterial perfusion sequence is a rare complication of monochorionic pregnancies that is characterized by the presence of an acardiac mass perfused by an apparently normal pump twin. The risk of death to the pump twin has led to a range of therapeutic interventions aimed at separating their vascular connection. We report a novel application of microwave ablation for vessel coagulation in the treatment of twin-reversed arterial perfusion sequence. MATERIAL AND METHODS: Microwave ablation has been adopted by surgical subspecialties as a superior energy source for vessel and tissue ablation as it creates heat without a circuit and has less thermal spread. We describe the use of a 2.45-GHz microwave system using a 1.8-mm antenna to coagulate the intra-abdominal portion of umbilical vessels of the acardiac mass. RESULTS: We report 6 cases of twin-reversed arterial perfusion sequence treated by microwave ablation. All patients were treated with microwave ablation with successful coagulation of intra-abdominal umbilical cord vessels of the acardiac mass with cessation of flow. DISCUSSION: Microwave ablation is an excellent energy source for vessel coagulation due to its thermal properties and can be used effectively in the treatment of twin-reversed arterial perfusion sequence.

Liver transplantation for acute liver failure at 11-week gestation with successful maternal and fetal outcome.

Acute liver failure (ALF) during pregnancy is very uncommon. Pregnancy-specific liver conditions like hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome and acute fatty liver of pregnancy can cause ALF at term or postpartum, but, typically occur during the third trimester. Most of these patients recover spontaneously after delivery, but, on occasion, they require liver transplantation in the postpartum period. However, ALF during the first and second trimester of pregnancy requiring antepartum liver transplantation is rare. Only fifteen cases of liver transplantation during pregnancy have been reported, and very few occurred during the first trimester. We report a Woman who developed acute liver failure during the first trimester of pregnancy and underwent successful liver transplantation at 11-week gestation, followed by successful delivery of the fetus at 30 weeks. To our knowledge, this is the earliest case of successful liver transplantation during pregnancy followed by successful fetal outcome. We discuss management of the patient and fetus before, during, and after liver transplantation and review the literature on antepartum liver transplant in pregnancy.

Combined sonographic and endoscopic umbilical cord occlusion in twin and triplet gestations.

OBJECTIVE: To review our experience with a minimally invasive technique for umbilical cord occlusion as a method of selective feticide in monochorionic sets. STUDY DESIGN: Umbilical cord occlusion was completed using 3 mm bipolar cautery under ultrasound guidance (3D/4D, n = 6; 2D, n = 6) with pre and post ligation endoscopic evaluation. RESULTS: 12 cases of monochorionic sets where selective feticide was performed were identified during the period 2000 to present. There were four triplet and eight twin gestations in the study cohort. Median interval from intervention to delivery was 16 weeks (range, 5-19). All co-twins survived the procedure and 15 of 16 were delivered after 33 weeks. CONCLUSIONS: Umbilical cord occlusion in monochorionic sets can be accomplished in a minimally invasive manner with combined endoscopic and ultrasound guidance in both twin and triplet pregnancies.

Thrombin-dependent regulation of matrix metalloproteinase (MMP)-9 levels in human fetal membranes.

OBJECTIVE: Amniochorion matrix metalloproteinase (MMP)-9 levels increase during labor, reaching a maximum in patients with preterm premature rupture of membranes (PPROM). Bleeding is a major risk factor for PPROM. Since such hemorrhage into the tissue factor-enriched decidua induces intense thrombin formation, we determined whether thrombin stimulates MMP levels in amniochorionic membranes. STUDY DESIGN: Fetal membrane (amniochorion) cultures were maintained in media with and without thrombin, lipopolysaccharide (LPS), thrombin receptor agonist peptide (TRAP)-14, and the anti-inflammatory steroid, dexamethasone (DEX). Concentrations of MMP-9, MMP-1, and tissue inhibitor of metalloproteinase (TIMP)-1 in culture media were measured by ELISA and normalized to total cell protein. RESULTS: The presence of thrombin induced MMP-9 levels. TRAP-14, a thrombin receptor agonist, also significantly increased MMP-9 levels, suggesting that thrombin-induced changes in MMP-9 expression were mediated through the thrombin receptor. Conversely, levels of MMP-1 and TIMP-1 were not affected by thrombin treatment, indicative of specificity of its action. The presence of LPS increased the concentration of MMP-9 and MMP-1. In contrast, DEX treatment significantly reduced MMP-9 levels. CONCLUSION: Our findings clearly demonstrated that thrombin treatment selectively increased the concentration of MMP-9 in culture media of amniochorionic membranes. Our results provide a potential mechanism through which alterations in hemostasis promote PPROM through thrombin-dependent stimulation of MMP-9.

Three-dimensional ultrasound to differentiate epigastric heteropagus conjoined twins from a TRAP sequence.

Twin reversed arterial perfusion sequence and epigastric heteropagus conjoined twins may appear similar antenatally. Three-dimensional ultrasound evaluated the relationship of a completely formed fetus and an adjacent second body consisting of a pelvis with 2 lower extremities, confirming the final diagnosis when two-dimensional ultrasound was unsuccessful. Three-dimensional ultrasound is useful in diagnosing epigastric heteropagus conjoined twins.

The closure of iatrogenic membrane defects after amniocentesis and endoscopic intrauterine procedures.

OBJECTIVE: To describe a new technique for wound closure after endoscopic intrauterine procedures which prevents amniotic fluid leakage after the procedure. STUDY DESIGN: This is an observational study which reviews a new technique under an IRB-approved protocol. The rationale for this study was the increasing frequency of intrauterine endoscopic procedures. The most common complication of these procedures is persistent leakage of amniotic fluid from puncture sites, which can result in preterm labor and preterm delivery. Thus, these procedures carry a high morbidity rate that may overcome the benefit of the intervention. We have employed a new technique, which has successfully prevented amniotic fluid leakage following the procedure. The instruments used for the endoscopic procedures were no larger than 3.5 mm for all cases. A sealant of platelets was rapidly injected followed by injection of fibrin glue and powdered collagen slurry at each puncture site. Sonography for modified AFI, clinical examination for nitrazine and ferning, and pad count were performed after each procedure at three intervals: immediately after the procedure, 24 h and 48 h. RESULTS: Eight patients undergoing an endoscopic intrauterine procedure (either cord ligation for twin-twin transfusion syndrome or sealing of ruptured membranes after amniocentesis) were included. All patients were treated between 18 and 24 weeks of gestation. Sonography, clinical examination and pad count revealed no evidence of amniotic fluid leakage either intra-abdominally or vaginally in any of the patients. There was 1 patient who ruptured membranes 12 h after the procedure due to severe vomiting. Another patient elected to terminate the pregnancy 48 h after the procedure without evidence of leakage. The remaining patients continued for 8 weeks or more without fluid leakage. CONCLUSION: The technique described, immediate sealing of puncture wounds following endoscopic intrauterine procedures, is effective in preventing amniotic fluid loss after the procedure.

Increased rates of chorioamnionitis with extra-amniotic saline infusion method of labor induction.

OBJECTIVE: Extra-amniotic saline infusion has been shown to be equal to or more efficacious than misoprostol, laminaria, dinoprostone, and prostaglandin estradiol for cervical ripening and labor induction. Because of the introduction of a foreign body into the uterus, extra-amniotic saline infusion may potentially cause increased rates of chorioamnionitis. This study examines the risk of chorioamnionitis with extra-amniotic saline infusion compared with other methods of induction and spontaneous labor. METHODS: A retrospective analysis was performed based on deliveries at Bellevue Hospital Center, a tertiary-care facility, from August 2000 to December 2002. Three groups were identified: extra-amniotic saline infusion, other methods of induction, and spontaneous labor. Differences in chorioamnionitis rates were analyzed by using analysis of variance and multivariable logistic regression as appropriate. RESULTS: There were 625 charts evaluated: 171 extra-amniotic saline infusion, 190 other, and 264 with spontaneous labor. The rates of chorioamnionitis were 26.9%, 17.9%, and 13.3%, respectively. After adjusting for confounding variables, such as instrumentation, length of rupture, and number of exams, subjects who were induced with extra-amniotic saline infusion were significantly more likely to develop chorioamnionitis (relative risk = 2.2; 95% confidence interval 1.4, 4.0; P =.006). CONCLUSION: Extra-amniotic saline infusion may be associated with a greater risk of chorioamnionitis when compared with other methods of labor induction. Given the increased risk of chorioamnionitis associated with extra-amniotic saline infusion, its use should be in the context of a careful assessment of the risks and benefits of various methods of labor induction. LEVEL OF EVIDENCE: II-2

Congenital laryngeal atresia associated with partial diaphragmatic obliteration.

OBJECTIVE: Laryngeal atresia is a rare, life-threatening congenital malformation. Prenatal sonographic diagnosis has been described; however, in many cases, the precise diagnosis is established only at autopsy. Our aim was to describe an atypical prenatal presentation of congenital laryngeal atresia in which the final diagnosis was made only at autopsy. METHODS: Sonographic and postmortem examinations were performed on a fetus with bilateral enlarged echogenic lung fields, an everted diaphragm, and polyhydramnios, which were initially noted on prenatal sonography at 26 weeks' gestation. RESULTS: Unfortunately, the mother was lost to follow up at our inner-city clinic, thus precluding a definitive diagnosis. At birth, tracheostomy was not performed because of the anomalous appearance of the neonate and the suspicion of multiple congenital anomalies. Neonatal death occurred after 18 minutes of life. Autopsy revealed laryngeal atresia with a right hemidiaphragmatic defect and multiple other congenital anomalies. CONCLUSIONS: This was a rare case with prenatal sonographic findings in a fetus with congenital laryngeal atresia associated with partial diaphragmatic obliteration.